The effect of oxygen at high pressure (OHP) will be examined on GABA and glutamate mediated synaptic transmission. Preliminary studies indicate that inhibitory transmission appears to fail during OHP while the spontaneous release of excitatory transmitter increases. The proposed experiments will investigate the failure of inhibitory transmission by examining inhibitory EPP amplitude, quantal content, reversal potential, resting postsynaptic membrane potential and effective resistance during OHP and pressure only controls. These measurements will be made on the walking leg neuromuscular preparation of the lobster. To test the possibility that a fall in GABA level is a primary factor in the action of OHP, agents which inhibit GAD (i.e., isoniazid) and which elevate GABA levels, (i.e., aminooxyacetic acid) will be used and the results compared to OHP alone. In addition, GAD activity will be measured using l4C-glutamate during OHP, pressure only, and isoniazid treatment. Postsynaptic inhibitory receptor function will be examined during OHP by exogenous application of GABA. Action of OHP on excitatory transmission will also be determined by examining the effect of OHP and pressure only on excitatory EPP amplitude, MEPP amplitude, MEPP frequency, quantal content and reversal potential. Since presynaptic Na ion accumulation due to failure of the Na-K pump may be a factor in the excitatory MEPP frequency increase seen during OHP, this possibility will be tested by examining the time to onset for frequency increase during OHP under conditions of lowered external Na ion concentrations and pretreatment with TTX. The role of the GABA shunt in the failure of th Na ion-K ion pump will be investigated by examining the effect of isoniazid, aminooxyacetic acid and succinate on MEPP frequency.